Synthesis of quinaldinium salts



Fatented July 21, 1953 SYNTHESIS OF QUINALDINIUM SALTS Donald W. Heseltina Rochester, N.,Y., assignorm to Eastman Kodak Company, Rochester, -N Y., a corporation of New Jersey No Drawing. Original application April 8, 1950, Serial No. 154,881. Divided and this'application May 19, 1951, Serial No. 227,273

This invention relates to a new method for preparing quinaldinium salts and to new quaternary salts obtained thereby.

It is known that quinaldine bases can be prepared by reacting together an aromatic primary amine and an aldehyde in the presence of an oxidizing agent and a hydrohalogen acid (Doebner 8 Claims. (Cl. 260- 286) 8: V. Miller, Ber. 14 (1881), 2816). While it iS known that some secondary amines, or a mixture of secondary'amines, are formed in this reaction.

by the reduction of the intermediate aldimines formed, no quaternary salt can be isolated.

I have now found that acid addition saltsof aromatic secondary amines can be reacted with. a1dehydes,. or compoundsgiving rise'thereto, in

the presence of an oxidizing agent to give, not a quinaldine base, but a quinaldinium salt.

,It is, therefore, an object'of my invention to provide a new method for preparing quinaldinium salts. Afurther object is to provide quinaldinium salts, some of which have not heretofore been known. Other objects will become apparent from a'consideration of the following description and examples. 1

According to my invention I provide a new process for preparing quinaldinium salts which comprises reacting an acid addition salt of an aromatic secondary amine with a compound selected from the group consisting of acetaldehyde, paraldehyde, aldol, and crotonaldehyde in the presence of an oxidizing agent. r e

.Ihe aromatic secondary amines ,whose acid ad, dition salts can be used in my invention comprise the N-alkylaryl amines, such as N-methylamline, N ethylaniline, N methyl-p-chloroaniline, N-, methyl-p-toluidine, etc., the diarylamines such as diphenylamine, p,p-ditolylamine, p,p-di chlorodiphenylamine, etc. and heterocyclicsecondary amines, such as tetrahydroquinoline, dihydroindole (indoline), carbazole, 3,4,5,6-tetrahydrocarbazole, phenothiazine (thiodiphenylamine), 2,3-trimethyleneindoline, etc. The acid addition salts of the N-alkylaryl and diaryl amines useful in practicing my invention can advantageously be represented by the following general formula:

CLELHX I D represents the nonmetallic atoms necessary to complete an aromatic nucleus, such as phenyl,

'o-,em-, and p-chlorophenyl, etc. (e. g. a mononuclear aryl group of the benzene series), and X represents an acid radical, e. g. chlorine, bromine,

iodine, sulfate, perchlorate, thiocyanate, alkyl .sulfate (e. g. methyl sulfate), toluenesulfonate,

etc.

The acid addition salts of the heterocyclic secondary amines useful in practicing my invention can advantageously be represented by the following general formula: I

wherein D1 represents the non-metallic atoms necessary to complete an aromatic nucleus, such as phenyl, chlorophenyl, hydroxyphenyl, etc. nuclei (efg. an aromatic nucleus of the benzene series), X has the meaning given above, and Z represents the non-metallic atoms necessary to complete a heterocyclic' nucleus containing from, 5to Gatomsin the heterocyclic ring, such as tetrahy'dropyrrole (II represents indoline type),l indole (II represents carbazole ortetrahydrocarbazoletype) ,benzothiazine (II represents pheno-- thiazine type), etc. nuclei." The aromatic nuclei can have substituted thereon Cl, Br, alkoxyl (e. g. methoxyl, etc.), hydroxyl, etc. groups, although,

as can be seen from the above general formulas,

at least one of the positionsortho to the secondary nitrogen atom in the compounds of Formula I, or peri to that of the secondary nitrogen atom in the compounds of Formula II, should be free of substituents.

As oxidizing agents I can advantageously use mononuclear nitroaromatic compounds of the benzene series, such as nitrobenzene, nitrotoluene,

' etc., nitroaromaticsulfonic acids, such as m-nitrobenzenesulfonic' acid," etc., nitrophenols, such as oand p-nitrophenoI, etc., ferric halides, such as ferric chloride, etc., arsenic pentoxide or arsenic acid,etc. Ordinary air can be used, although less advantageously than the conventional oxidizing agents set out above. Instead of employing the acid addition salt of the secondary amine as such, according'tothe method'des'c'ribed above and in certain of the following examples, the secondary amine can be suspended in an aqueous-solution of an acid, and the reaction carried out in thismedium. Under these conditions the acid forms an addition salt with the secondary-amine, and the latter undergoes condensation with the aldehyde. If a poly--" meric aldehyde is employed (e. g. paraldchyde),

the acid performs a dual purpose, since it serves to decompose the polymeric aldehyde into the cor:- responding monomer, which undergoes reaction with the acid addition salt. Hydrochloric or sulfuric acids have been found to provide aqueous solutions which are excellently adapted as reaction media for' the process of my invention. A condensation agent or catalyst, such as zinc chloride, etc. can be added to the reaction mix='-- ture, although this is not necessary...

The reaction can be carried out at' room temperature (about 25 C.) orgatttemperaturesras:

cording to the process of my invention are those.

represented by the following general formulas:

wherein R1 represents a: mononuclear aromatic nucleus of the benzene series, Z1 represents the non-metallic; atoms; necessary to. complete: a,- heterocyclicv nucleus of, the 2-1-quinolineseries,1 X'

hasgthe value setforth, aboye zzarepresents the.

non-metallic atomsnecessary tocomplete a heterocyclic nucleus ofthe'pyridine series, Dr-has. the value set forth above,,and-. n representsa positive integer from 21110 3.

The following examples-wilLserve z to. illustrate:

further the mannerrwhereby I'practicerny-inven-- tion;

Example 1'.-1 ,8- trimethylenequi7raldinium iodide 60. g; of tetrahydroquinoline hydrochloride (MW=170) and 115 g. of ferric. chloride (MW=162) were dissolved in 400 cc. of absolute.

, mixture-by: distillation, and the salts taken upin three liters of hot water.. The aqueous solution. was madeslightly alkaline. with 40 per cent sodium hydroxide, and precipitated hydroxides were filtered off. The filtrate wastreated with'20 g. of; sodium iodide,(MW==150) and takento. dry:-

ness under reduced. pressure. Thecombined salts.

were extracted with 500 cc. of ethyl alcohol, and the alcoholic solution concentrated to 100 cc. and chilled. The 1,8-trimethylenequinaldinium iodide was filtered off and recrystallized from ethyl alcohol. There were thus obtained 22 g. of pure salt,,representing,a 20 per centiyieldl.

When a molecularly equivalent'amount of the hydrochloride of carbazole is substituted for the *tetrahydroquinoline hydrochloride used in the above example; aouaternary salt represented by the following formula can be obtained:

Also, it is possible to use to advantage aldol in place:ofrtheparaldehyde- Easample 2;1 methylquinaldiniumperchlorate 53 g. of'JNfi-i-methylaniline (MW=107)3 were:

solved. in 200 cc; of concentrated hydrochloric; acid, and35g; of o;-nitrophenol..were':add'ed;. The. reaction mixturezwas heated .to: refluxmwithastirringv andi132'ig3 ofi paraldehydez (Mitr 132) were;

added: dropwise over? a two-hour periodi. The:

aqueous portion was decanted from. the :tar; and the tar washediwithanadditionaltZOO cc'z-offhot water. The: combined: aqueous:- extracts, were chilled, filtered, andlwash'ed with benzene; The 40 waterportion was 'mixed with decolorizing car bon, shaken filtered, andevaporated to dryness: under reduced pressure. The-:- residue was e tractedw-ith 100cc; of -wat'er neutralized with an aqueous solution of sodium carbonate, and; ex:- tracted with chloroform; The aqueous: portion was mixed with decolorizingrarbon, shaken, and. filtered. The quaternary salt was then Y. precipi tated by the additionof 20s; of sodiunr perchlo rate, filteredoif" and dried: After'recrystallization from" ethyl alcohol, 10.1: g; of"1 -methy1-- quinaldinium perchlorate, representingan 8" per cent yield were obtained. It -melted am -154- 156 C';

Whena molecularly equivalent amount 'of N m'ethyl p chloroaniline replaces the; N methylaniline milie above example, a quaternary; altrepresented" by; the following formula: can be obtained? Example 3.-1,8-EthyZeneqruinalcliniumiodide 200' cc. of; concentrated hydrochloric acid; and:

ii I if 51 g of .-m-nitrob.enzene sulfonic acid (MW=203) were added. The reaction-mixture was brought to reflux and 13-2 g. of paraldehyde (MW,=132) added dropwise with stirring over a period of two hours. The heating was then continued for twelve hours. The aqueous portion was decanted and the residue extracted withtwoliters of boiling water. The combined aqueous portions were neutralized I with aqueous sodium carbonate, extracted with benzene, mixed with decolorizing carbon, and filtered. 30 g. of sodium iodide -(MW==150) were added and the aqueous solution evaporated to dryness under reduced pressure. The combined salts were extracted with 500 cc. ,of hot absolute ethyl alcohol.

and chilled. The filtercake was then dried to give 30 g. of .1,B-ethylenequinaldinium iodide, representing a 20.1p'e1 cent yield. It melted at 254-255 C. with decomposition- When a molecularly equivalent amountof 2,3-

trimethylene-indoline replaces the indoline in the above example, a quaternary salt represented by the following formula can be obtained:

Example 4.1-Piz.en-ylquinaldinium perchlorate CH: N/

84.5 g. of diphenylamine (MW=169) were dissolved in 400 cc. of nitrobenzene, and 49 g. of

sulfuric acid were added dropwise with stirring.

I ized with sodium carbonate, extracted with benzene,'and 30 g. of sodium iodide (MW=150) were added. The Water solution was evaporated to dryness, and the product extracted from the salts with 400 cc. of hot absolute ethyl alcohol. The alcohol solution was concentrated to 75 cc. and chilled. The l-phenylquinaldinium salt was thrown out of solution by the addition of ether. The precipitated salt was then dissolved in 20 cc. of water and precipitated by the addition of g. of sodium perchlorate. The product was filtered off, and after recrystallization from water gave 7.5 g. of l-phenylquinaldinium perchlorate. It melted at 160-l62 C. with decomposition.

When a molecularly equivalent amount of phenothiazine replaces the diphenylaminein the The alcohol extracts were concentrated to 150 cc; mixed with decolorizing carbon, shaken, filtered,

above example, a quaternary salt represented by the following formula can be obtained:

Operating in a manner similarrto that illustrated above, other quinaldinium salts can be prepared according to the process of my invention. The quinaldinium salts prepared according to the process of 'my invention can be used in the preparation of other useful materials, such as polymethine dyes, as described in the applica- R-NH6 CHHX wherein R represents a member selected from the group consisting of an alkyl group and an' aryl group, D represents the non-metallic atoms necessary to complete an aromatic nucleus, and X represents an acid radical, with a compound selected'from the group consisting of acetaldehyde, paraldehyde, aldol, and crotonaldehyde, in the presence of an oxidizing agent.

2. A process for preparing quinaldinium quaternary salts comprising condensing a compound selected from those represented by the following general formula:

I R NH-o' oH.Hx wherein R. represents a mononuclear aryl group of the, benzene series, D represents the nonmetallic atoms necessary to complete a mononuclear aryl group of the benzene series, and X represents an acid radical, with crotonaldehyde in the presence of an oxidizing agent.

3. A process for preparing quinaldinium quaternary salts comprising condensinga compound selected from those represented by the following general formula: v r I R-NH-d 2311px wherein R represents an alkyl group containing from 1 to 2 carbon atoms, D represents the nonmetallic atoms necessary to complete a mononuclear aryl group of the benzene series, and X represents an acid radical, with paraldehyde in g the presence of an oxidizing agent.

4. A process for preparing quinaldinium quaternary salts comprising condensing a compound selected from those represented by the following general formula:

wherein R, represents a mononucleararyl group of the benzene series, D represents the nonmetallic atoms .inecessary to complete ;a :moncnuclear aryl groupof the benzene series, andrX represents an acid radical, with crotonaldehyde in the presence of a mononuclear, nitroaromatic compound of the benzene series.

5. A process for preparing quinaldinium quaternary salts comprising condensing a compound selected from those represented by the following general formula:

R-NH- CHBX wherein R represents an alkyl group containin from 1 to 2 carbon atoms, D-represents the nonmetallic atoms necessary to complete a 'mononuclear arylgroup of the benzene-series, and X represents an acid radical, with p-a-raldehyde the presence of a mononuclear. nitroaromatic compound of the benzene series.

6. A process forpreparing quinaldinium quaternary salts comprising condensing a compound selected from those representedby the-following general formula:

ternary salts comprising condensing a compound selected from those represented by .the following general formul'az Referencescited in the 'file of this patent UNITED STATES PATENTS Number Name Date 2,158,287 Konlg May 16, 1939 2,536,973 Anisn Jan. 2, 1951 FOREIGN PATENTS Number Country Date 710,748 Germany Sept. 20, 1941 OTHER REFERENCES Fieser et al., Organic Chemistry (D. C. Heath and Company; 1944; Boston), page 32. 

1. A PROCESS FOR PREPARING QUINALDINIUM QUATERNARY SALTS COMPRISING CONDENSING A COMPOUND SELECTED FROM THOSE REPRESENTED BY THE FOLLOWING GENERAL FORMULA: 